Galectin-3, a marker of cardiac fibrosis, is associated with an increased risk of heart failure and death, researchers found.

Action Points

Explain that a study using the Framingham Heart Study offspring cohort found Galectin-3 protein, a marker of cardiac fibrosis, was predictive of later development of heart failure.

Note that when added to other clinical factors, net classification was only marginally improved.

Galectin-3 (Gal-3), a marker of cardiac fibrosis, is associated with an increased risk of heart failure and death, researchers found.

Over a mean follow-up of nearly 9 years, those with elevated levels of Gal-3 had a significant 28% (95% CI 1.14 to 1.43, P<0.0001) increased risk of developing heart failure when adjusted for age and sex, reported Daniel Levy, MD, and colleagues from the National Heart, Lung, and Blood Institute in Bethesda, Md.

High levels of the protein were also associated with a significant 24% (95% CI 1.12 to 1.38, P<0.0001) increased risk of all-cause death, according to the study published online in the Journal of the American College of Cardiology.

"This collective experimental evidence suggests that Gal-3 may play a causal in cardiac remodeling," the authors stated.

However, adding Gal-3 to clinical factors resulted in only minor improvements in net reclassification. It also did not substantially increase the C-statistic (0.855 to 0.859).

Nonetheless, this is the first time that it's been shown that Gal-3 has a relationship with future heart failure, noted David Morrow, MD, MPH, and Michelle O'Donoghue, MD, MPH, of Brigham and Women's Hospital in Boston, in an accompanying editorial.

Although Gal-3 has been associated with adverse events in those with heart failure, it has not been evaluated as a predictor of incident heart failure in apparently healthy people.

Cardiac fibrosis, of which Gal-3 is a marker, plays an important role in the development of heart failure. Earlier identification of elevated levels of this betagalactoside-binding lectin might offer the opportunity to treat people long before heart failure develops, researchers said.

To fill in the gap, Levy and colleagues evaluated 3,353 participants enrolled in the offspring cohort of the community-based Framingham Heart Study.

The mean age of participants was 59 and 53% of them were women. Overall, Gal-3 levels were higher in women than men (median 14.3 ng/mL versus 13.1 ng/mL, P<0.05).

Also, those with higher concentrations of the protein tended to be older and have more cardiovascular risk factors such as high blood pressure, diabetes, previous coronary artery disease, a higher body mass index, and a lower estimated glomerular filtration rate (eGFR; P<0.0001, for the trend for all).

When researchers performed a multivariate analysis, only eGFR was dropped from the list of risk factors above, while B-type natriuretic peptide (BNP) was added.

Examining the echocardiographic data, researchers found Gal-3 was significantly associated with positive left ventricular remodeling. Having higher levels of the protein conferred twice the odds of having elevated left ventricular mass, they wrote.

But Gal-3 was not associated with fractional shortening, left ventricular systolic dysfunction, or left atrial size.

During a mean follow-up period of 8.1 years, 5.1% of patients experienced ﬁrst heart failure events.

The upper limits for Gal-3 quartiles for men and women were 15.4 ng/ml to 47.7 ng/ml and 16.8 ng/ml to 52.1 ng/ml, respectively. The lower limits were 3.9 ng/ml to 11.1 ng/ml for men and 5.0 ng/ml to 12.0 ng/ml for women.

Among the 25% of people with the highest Gal-3 levels, the annual rate of heart failure was 12 per 1,000 person-years compared with 3 per 1,000 person-years for the 25% of participants with the lowest levels.

Researchers added BNP to the multivariate analysis and found that high Gal-3 levels increased the risk of a first heart failure incident by a significant 23%. However, BNP was associated with a significant 46% increased risk.

There was no difference regarding Gal-3 levels between those with preserved ejection fraction and depressed ejection fraction.

Levy and colleagues suggested that directly modulating that Gal-3 pathway may be beneficial in these patients. They called for more study into how assessment of Gal-3 can help this patient population.

Morrow and O'Donoghue noted that Gal-3 is also sensitive to fibrotic conditions in other areas such as the liver, lungs, and kidneys. For that reason, it may difficult to include the protein in a screening strategy.

Study limitations included the modest number of heart failure events and the possibility that Gal-3 levels are influenced by other conditions. Also, the results may not be generalizable because patients were mostly Caucasian.